title: Resveratrol inhibits hydrogen peroxide-induced apoptosis in endothelial cells via the activation of PI3K/Akt by miR-126.
abstract: OBJECTIVE
  Resveratrol(RSV) is an edible polyphenolic phytoalexin present in different plant species that plays an important role in improving endothelial dysfunction. However, the molecular mechanisms underlying these effects are unknown. In the present study, the mechanism underlying the protection of CRL-1730 cells by RSV against oxidative stress was examined.
  
  
  METHODS
  We first assessed the effects of RSV on the cell viability and apoptosis of CRL-1730 cells exposed to hydrogen peroxide(H2O2). Real-time PCR was used to determine the microRNA-126(miR-126) expression in cells treated with RSV and/or H2O2. We also evaluated the PI3K/Akt signaling pathway in CRL-1730 cells following upregulation of the miR-126 expression. Finally, we determined the effects of miR-126 on RSV against oxidative injury using an miR-126 inhibitor.
  
  
  RESULTS
  Treatment with RSV resulted in a significant increase in survival and a decrease in the apoptosis of CRL-1730 cells exposed to H2O2. We also found that H2O2 significantly suppressed the expression of miR-126, which was reversed by RSV in a dose-dependent manner. The overexpression of miR-126 decreased PIK3R2(p85-β) and enhanced Akt phosphorylation, which resulted in an increase in the survival of CRL-1730 cells exposed to H2O2. More importantly, the downregulation of the miR-126 expression reversed the effects of RSV on the survival and apoptosis of CRL-1730 cells exposed to H2O2. In addition, the knockdown of Ets-1 reversed the effects of RSV on the miR-126 expression in CRL-1730 cells exposed to H2O2.
  
  
  CONCLUSIONS
  In this study, we demonstrated that the protection of endothelial cells by RSV against oxidative injury is due to the activation of PI3K/Akt by miR-126.
authors.affiliation: Department of Cardiology, Hangzhou Red Cross Hospital.
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Sui
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Xu
authors.forename: Ming-Bin
authors.initials: MB
authors.lastname: Xie
authors.forename: De-An
authors.initials: DA
authors.lastname: Pei
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D016877:Oxidants; D012333:RNA, Messenger; D013267:Stilbenes; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol